Nociceptin (the same substance as orphanin FQ) is peptide comprising 17 amino acids and having a similar structure to that of opioid peptide. Nociceptin has an augmenting activity on reaction against nociceptive stimulation, an appetite stimulating activity, an activity for reducing a space learning ability, an antagonism against an analgesic action of a classic opiate agonist, a dopamine release inhibitory action, a water diuresis action, a vasodilative action, and a systemic blood pressure-lowering action, and it is considered to take part in controlling pain, appetite and memory learning through a nociceptin receptor ORL1 [refer to Nature, vol. 377, pp. 532 (1995); Society for Neuroscience, vol. 22, pp. 455 (1996);
NeuroReport, vol. 8, pp. 423 (1997); Eur. J. Neuroscience, vol. 9, pp. 194 (1997); Neuroscience, vol. 75, pp. 1 and 333 (1996); and Life Science, vol. 60, pp. PL15 and PL141 (1997)]. Further, it is known that morphine tolerance is reduced in a knockout mouse in which a nociceptin receptor ORL1 is deficient [Neuroscience Letters, vol. 237, pp. 136 (1997)].
Accordingly, it can be expected that a substance which specifically prevents nociceptin from binding to a nociceptin receptor ORL1 is useful as an analgesic against diseases accompanied with pains such as cancerous pain, postoperative pain, migraine, gout, chronic rheumatism, chronic pain and neuralgia, a reliever against tolerance to a narcotic analgesic represented by morphine, a reliever against dependence on a narcotic analgesic represented by morphine, an analgesic enhancer, an antiobestic, a drug for ameliorating brain function, a remedy for schizophrenia, a remedy for Parkinsonism, a remedy for chorea, an antidepressant, a remedy for diabetes insipidus, a remedy for polyuria, or a remedy for hypotension.
A compound which is structurally similar to the compound of the present invention is disclosed in International Publication WO96 /13262 and the like. However, the compound of the present invention is neither specifically disclosed nor indicated, and an action to prevent nociceptin from binding to a nociceptin receptor ORL1 is not entirely described as well.